n(6)-(1-carboxyethyl)lysine and Inflammation

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to the formation of advanced glycation end-products (AGEs). In this study we investigated in 88 COPD patients and 55 control subjects (80% ex-smokers) the association of the plasma protein-bound AGEs N(ε)-(carboxymethyl)lysine (CML), pentosidine, N(ε)-(carboxyethyl)lysine (CEL), and AGE accumulation in skin by skin autofluorescence (AFR), with lung function. Mean ± sd plasma CML was decreased (COPD 61.6 ± 15.6 nmol · mmol(-1) lysine, never-smokers 80.7 ± 19.8 nmol · mmol(-1) lysine and ex-smokers 82.9 ± 19.3 nmol · mmol(-1) lysine) and CEL (COPD 39.1 ± 10.9 nmol · mmol(-1) lysine, never-smokers 30.4 ± 5.0 nmol · mmol(-1) lysine and ex-smokers 27.7 ± 6.4 nmol · mmol(-1) lysine) and AFR (COPD 3.33 ± 0.67 arbitrary units (AU), never-smokers 2.24 ± 0.45 AU and ex-smokers 2.31 ± 0.47 AU) were increased in COPD patients compared to controls. Disease state was inversely associated with CML, and linearly associated with CEL and AFR. Performing regression analyses in the total group, CEL and AFR showed a negative association and CML a positive association with lung function, even after correction for potential confounders. In conclusion, CEL and AFR were negatively and CML was positively associated with disease state. In the total group only the AGEs showed an association with forced expiratory volume in 1 s. Our data suggest that AGEs are involved in the pathophysiology of COPD, although their exact role remains to be determined.

Topics: Aged; Arginine; Case-Control Studies; Female; Fluorescence; Glycation End Products, Advanced; Humans; Inflammation; Lung; Lysine; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Skin; Smoking; Spirometry

Nepsilon-carboxymethyllysine (CML) is the major non-cross linking advanced glycation end product (AGE). CML is elevated in diabetic patients and apparent in atherosclerotic lesions. AGEs are associated with hypertension and arterial stiffness potentially by qualitative changes of elastic fibers. We investigated whether CML affects carotid and aortic properties in normoglycemic subjects.. Hundred-two subjects (age 48.2+/-11.3 years) of the FLEMENGHO study were stratified according to the median of the plasma CML level (200.8 ng/ml; 25th percentile: 181.6 ng/ml, 75th percentile: 226.1 ng/ml) into "high CML" versus "low CML" as determined by ELISA. Local carotid artery properties, carotid intima media thickness (IMT), aortic pulse wave velocity (PWV), blood pressure and fetuin-A were analyzed. In 26 patients after carotidectomy, CML was visualized using immunohistochemistry.. According to the CML median, groups were similar for anthropometric and biochemical data. Carotid diameter was enlarged in the "high" CML group (485.7+/-122.2 versus 421.2+/-133.2 microm; P<0.05), in particular in participants with elevated blood pressure and with "high" CML ("low" CML: 377.9+/-122.2 microm and "high" CML: 514.5+/-151.6 microm; P<0.001). CML was associated fetuin-A as marker of vascular inflammation in the whole cohort (r=0.28; P<0.01) and with carotid diameter in hypertensive subjects (r=0.42; P<0.01). CML level had no effect on aortic stiffness. CML was detected in the subendothelial space of human carotid arteries.. In normoglycemic subjects CML was associated with carotid diameter without adaptive changes of elastic properties and with fetuin-A as vascular inflammation marker, in particular in subjects with elevated blood pressure. This may suggest qualitative changes of elastic fibers resulting in a defective mechanotransduction, in particular as CML is present in human carotid arteries.

Topics: Adult; alpha-2-HS-Glycoprotein; Anthropometry; Belgium; Biomarkers; Blood Proteins; Carotid Arteries; Carotid Artery Diseases; Cohort Studies; Elasticity; Female; Glycation End Products, Advanced; Humans; Hypertension; Inflammation; Lysine; Male; Mechanotransduction, Cellular; Middle Aged; Sampling Studies; Tunica Intima; Ultrasonography